CA2560108A1 - Acides nucleiques immunostimulateurs destines a induire des reactions d'il-10 - Google Patents

Info

Publication number

CA2560108A1

CA2560108A1 CA002560108A CA2560108A CA2560108A1 CA 2560108 A1 CA2560108 A1 CA 2560108A1 CA 002560108 A CA002560108 A CA 002560108A CA 2560108 A CA2560108 A CA 2560108A CA 2560108 A1 CA2560108 A1 CA 2560108A1

Authority

CA

Canada

Prior art keywords

oligonucleotide

subject

cytosine

modified

nucleotide

Prior art date

2004-04-02

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 102000039446 nucleic acids Human genes 0.000 title claims abstract description 130
• 108020004707 nucleic acids Proteins 0.000 title claims abstract description 130
• 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 124
• 230000003308 immunostimulating effect Effects 0.000 title claims abstract description 74
• 230000001939 inductive effect Effects 0.000 title claims abstract description 19
• 230000004044 response Effects 0.000 title claims description 27
• CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 claims abstract description 91
• 102000003814 Interleukin-10 Human genes 0.000 claims abstract description 67
• 108090000174 Interleukin-10 Proteins 0.000 claims abstract description 67
• 238000000034 method Methods 0.000 claims abstract description 59
• 230000014509 gene expression Effects 0.000 claims abstract description 24
• 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 15
• 108091034117 Oligonucleotide Proteins 0.000 claims description 159
• 125000003729 nucleotide group Chemical group 0.000 claims description 96
• 239000002773 nucleotide Substances 0.000 claims description 94
• 239000000427 antigen Substances 0.000 claims description 83
• 102000036639 antigens Human genes 0.000 claims description 83
• 108091007433 antigens Proteins 0.000 claims description 83
• 239000000203 mixture Substances 0.000 claims description 59
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 38
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 38
• -1 2-mercapto-cytosine Chemical compound 0.000 claims description 34
• 208000023275 Autoimmune disease Diseases 0.000 claims description 31
• 108091033319 polynucleotide Proteins 0.000 claims description 27
• 239000002157 polynucleotide Substances 0.000 claims description 27
• 102000040430 polynucleotide Human genes 0.000 claims description 27
• 230000001965 increasing effect Effects 0.000 claims description 23
• 229940104302 cytosine Drugs 0.000 claims description 22
• 239000007943 implant Substances 0.000 claims description 22
• 102000004127 Cytokines Human genes 0.000 claims description 20
• 108090000695 Cytokines Proteins 0.000 claims description 20
• 150000004713 phosphodiesters Chemical class 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 18
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical class O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 12
• 230000001404 mediated effect Effects 0.000 claims description 12
• 125000003118 aryl group Chemical group 0.000 claims description 11
• 208000015181 infectious disease Diseases 0.000 claims description 11
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical class N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 10
• 230000036755 cellular response Effects 0.000 claims description 10
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 9
• 208000026935 allergic disease Diseases 0.000 claims description 9
• 208000006673 asthma Diseases 0.000 claims description 9
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical class CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 9
• 210000002707 regulatory b cell Anatomy 0.000 claims description 9
• RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims description 8
• PNWOYKVCNDZOLS-UHFFFAOYSA-N 6-amino-5-chloro-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1Cl PNWOYKVCNDZOLS-UHFFFAOYSA-N 0.000 claims description 8
• 208000011231 Crohn disease Diseases 0.000 claims description 8
• 206010020751 Hypersensitivity Diseases 0.000 claims description 8
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 8
• 229940124597 therapeutic agent Drugs 0.000 claims description 8
• 230000005867 T cell response Effects 0.000 claims description 7
• 239000013566 allergen Substances 0.000 claims description 7
• 230000007815 allergy Effects 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 7
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 6
• NLLCDONDZDHLCI-UHFFFAOYSA-N 6-amino-5-hydroxy-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1O NLLCDONDZDHLCI-UHFFFAOYSA-N 0.000 claims description 6
• RGKBRPAAQSHTED-UHFFFAOYSA-N 8-oxoadenine Chemical compound NC1=NC=NC2=C1NC(=O)N2 RGKBRPAAQSHTED-UHFFFAOYSA-N 0.000 claims description 6
• 229930024421 Adenine Chemical class 0.000 claims description 6
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Chemical class OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
• 229960000643 adenine Drugs 0.000 claims description 6
• XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 claims description 6
• 229960004413 flucytosine Drugs 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 201000006417 multiple sclerosis Diseases 0.000 claims description 6
• 206010028417 myasthenia gravis Diseases 0.000 claims description 6
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical class N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 6
• MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical class NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims description 5
• OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 claims description 5
• TVICROIWXBFQEL-UHFFFAOYSA-N 6-(ethylamino)-1h-pyrimidin-2-one Chemical compound CCNC1=CC=NC(=O)N1 TVICROIWXBFQEL-UHFFFAOYSA-N 0.000 claims description 5
• MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical class NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 230000009885 systemic effect Effects 0.000 claims description 5
• LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 4
• QFVKLKDEXOWFSL-UHFFFAOYSA-N 6-amino-5-bromo-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1Br QFVKLKDEXOWFSL-UHFFFAOYSA-N 0.000 claims description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
• 208000003807 Graves Disease Diseases 0.000 claims description 4
• 208000015023 Graves' disease Diseases 0.000 claims description 4
• 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 4
• 201000011152 Pemphigus Diseases 0.000 claims description 4
• 206010039710 Scleroderma Diseases 0.000 claims description 4
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 239000002246 antineoplastic agent Substances 0.000 claims description 4
• 229960002949 fluorouracil Drugs 0.000 claims description 4
• 235000013305 food Nutrition 0.000 claims description 4
• 201000001976 pemphigus vulgaris Diseases 0.000 claims description 4
• 208000005987 polymyositis Diseases 0.000 claims description 4
• 229940035893 uracil Drugs 0.000 claims description 4
• GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 claims description 3
• YDBCQGNEXYFIHD-UHFFFAOYSA-N 1-methyl-1,2,4-triazole-3-carboxamide Chemical compound CN1C=NC(C(N)=O)=N1 YDBCQGNEXYFIHD-UHFFFAOYSA-N 0.000 claims description 3
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 claims description 3
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
• XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims description 3
• CRYCZDRIXVHNQB-UHFFFAOYSA-N 2-amino-8-bromo-3,7-dihydropurin-6-one Chemical class N1C(N)=NC(=O)C2=C1N=C(Br)N2 CRYCZDRIXVHNQB-UHFFFAOYSA-N 0.000 claims description 3
• LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 claims description 3
• BLXGZIDBSXVMLU-OWOJBTEDSA-N 5-[(e)-2-bromoethenyl]-1h-pyrimidine-2,4-dione Chemical compound Br\C=C\C1=CNC(=O)NC1=O BLXGZIDBSXVMLU-OWOJBTEDSA-N 0.000 claims description 3
• JGOFIFQGVZKYOL-UHFFFAOYSA-N 5-amino-3-methyl-4h-[1,3]thiazolo[4,5-d]pyrimidine-2,7-dione Chemical class N1=C(N)NC(=O)C2=C1N(C)C(=O)S2 JGOFIFQGVZKYOL-UHFFFAOYSA-N 0.000 claims description 3
• MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 claims description 3
• OFJNVANOCZHTMW-UHFFFAOYSA-N 5-hydroxyuracil Chemical compound OC1=CNC(=O)NC1=O OFJNVANOCZHTMW-UHFFFAOYSA-N 0.000 claims description 3
• OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 claims description 3
• UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 claims description 3
• UFVWJVAMULFOMC-UHFFFAOYSA-N 6-amino-5-iodo-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1I UFVWJVAMULFOMC-UHFFFAOYSA-N 0.000 claims description 3
• CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 claims description 3
• CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical class O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 claims description 3
• LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 claims description 3
• 208000035473 Communicable disease Diseases 0.000 claims description 3
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 3
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 3
• 229930010555 Inosine Chemical class 0.000 claims description 3
• SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical class O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 claims description 3
• 208000031845 Pernicious anaemia Diseases 0.000 claims description 3
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 3
• 125000004122 cyclic group Chemical group 0.000 claims description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical class C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
• 229960003786 inosine Drugs 0.000 claims description 3
• PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 3
• 230000000241 respiratory effect Effects 0.000 claims description 3
• 238000007920 subcutaneous administration Methods 0.000 claims description 3
• 229960003087 tioguanine Drugs 0.000 claims description 3
• OWIRVNDMYDSKIJ-UHFFFAOYSA-N 2,4-dichloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1Cl OWIRVNDMYDSKIJ-UHFFFAOYSA-N 0.000 claims description 2
• SXIYEPVAXKIRKQ-UHFFFAOYSA-N 6-amino-5-(difluoromethyl)-1h-pyrimidin-2-one Chemical compound NC1=NC(=O)NC=C1C(F)F SXIYEPVAXKIRKQ-UHFFFAOYSA-N 0.000 claims description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 2
• 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims description 2
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 2
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 2
• 208000007465 Giant cell arteritis Diseases 0.000 claims description 2
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 2
• 208000016604 Lyme disease Diseases 0.000 claims description 2
• 108091081548 Palindromic sequence Proteins 0.000 claims description 2
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 208000006045 Spondylarthropathies Diseases 0.000 claims description 2
• 206010047112 Vasculitides Diseases 0.000 claims description 2
• 206010047115 Vasculitis Diseases 0.000 claims description 2
• 206010047642 Vitiligo Diseases 0.000 claims description 2
• 210000004100 adrenal gland Anatomy 0.000 claims description 2
• 201000009961 allergic asthma Diseases 0.000 claims description 2
• 206010003246 arthritis Diseases 0.000 claims description 2
• 201000004339 autoimmune neuropathy Diseases 0.000 claims description 2
• 208000006424 autoimmune oophoritis Diseases 0.000 claims description 2
• 201000004982 autoimmune uveitis Diseases 0.000 claims description 2
• 230000001413 cellular effect Effects 0.000 claims description 2
• 229940127089 cytotoxic agent Drugs 0.000 claims description 2
• 201000001981 dermatomyositis Diseases 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 229940076263 indole Drugs 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 201000005737 orchitis Diseases 0.000 claims description 2
• 230000003439 radiotherapeutic effect Effects 0.000 claims description 2
• 201000005671 spondyloarthropathy Diseases 0.000 claims description 2
• 206010043207 temporal arteritis Diseases 0.000 claims description 2
• 230000000699 topical effect Effects 0.000 claims description 2
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims 1
• 206010009900 Colitis ulcerative Diseases 0.000 claims 1
• 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
• 230000028993 immune response Effects 0.000 abstract description 16
• 230000001276 controlling effect Effects 0.000 abstract 1
• 230000001737 promoting effect Effects 0.000 abstract 1
• 230000029069 type 2 immune response Effects 0.000 abstract 1
• 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 89
• 229940046166 oligodeoxynucleotide Drugs 0.000 description 60
• 229940076144 interleukin-10 Drugs 0.000 description 58
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 35
• 210000004027 cell Anatomy 0.000 description 32
• 238000009472 formulation Methods 0.000 description 30
• 108091029430 CpG site Proteins 0.000 description 24
• 230000000638 stimulation Effects 0.000 description 24
• 210000003719 b-lymphocyte Anatomy 0.000 description 23
• 150000001875 compounds Chemical class 0.000 description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
• 230000000694 effects Effects 0.000 description 20
• 230000031261 interleukin-10 production Effects 0.000 description 20
• 201000010099 disease Diseases 0.000 description 19
• 230000004936 stimulating effect Effects 0.000 description 17
• 235000000346 sugar Nutrition 0.000 description 17
• 238000004519 manufacturing process Methods 0.000 description 16
• 150000003839 salts Chemical class 0.000 description 15
• 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 14
• 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 14
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
• 230000028327 secretion Effects 0.000 description 14
• 230000001225 therapeutic effect Effects 0.000 description 14
• 101150014604 cpg-3 gene Proteins 0.000 description 13
• 102000004889 Interleukin-6 Human genes 0.000 description 12
• 108090001005 Interleukin-6 Proteins 0.000 description 12
• 230000004048 modification Effects 0.000 description 12
• 238000012986 modification Methods 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 206010028980 Neoplasm Diseases 0.000 description 11
• 229920002472 Starch Polymers 0.000 description 11
• 239000006228 supernatant Substances 0.000 description 11
• 108020004414 DNA Proteins 0.000 description 10
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 10
• 235000019698 starch Nutrition 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 238000002965 ELISA Methods 0.000 description 9
• 108010010803 Gelatin Proteins 0.000 description 9
• 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 9
• 201000011510 cancer Diseases 0.000 description 9
• 239000008273 gelatin Substances 0.000 description 9
• 229920000159 gelatin Polymers 0.000 description 9
• 229940014259 gelatin Drugs 0.000 description 9
• 235000019322 gelatine Nutrition 0.000 description 9
• 235000011852 gelatine desserts Nutrition 0.000 description 9
• 230000006698 induction Effects 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 101000800479 Homo sapiens Toll-like receptor 9 Proteins 0.000 description 8
• 239000000443 aerosol Substances 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 239000000243 solution Substances 0.000 description 8
• 229940032147 starch Drugs 0.000 description 8
• 239000008107 starch Substances 0.000 description 8
• 239000004094 surface-active agent Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• 239000000969 carrier Substances 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 125000005647 linker group Chemical group 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 229920001223 polyethylene glycol Polymers 0.000 description 7
• 150000003212 purines Chemical class 0.000 description 7
• 230000001105 regulatory effect Effects 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
• 239000005089 Luciferase Substances 0.000 description 6
• 241001529936 Murinae Species 0.000 description 6
• 230000001363 autoimmune Effects 0.000 description 6
• 239000001768 carboxy methyl cellulose Substances 0.000 description 6
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 239000007884 disintegrant Substances 0.000 description 6
• 102000045710 human TLR9 Human genes 0.000 description 6
• 239000002502 liposome Substances 0.000 description 6
• 210000000056 organ Anatomy 0.000 description 6
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 6
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
• 210000002784 stomach Anatomy 0.000 description 6
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 5
• 102000002227 Interferon Type I Human genes 0.000 description 5
• 108010014726 Interferon Type I Proteins 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 239000002671 adjuvant Substances 0.000 description 5
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 230000015556 catabolic process Effects 0.000 description 5
• 238000007385 chemical modification Methods 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 238000006731 degradation reaction Methods 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 230000036039 immunity Effects 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000004005 microsphere Substances 0.000 description 5
• 239000006199 nebulizer Substances 0.000 description 5
• 229920000642 polymer Polymers 0.000 description 5
• 230000003389 potentiating effect Effects 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 150000008163 sugars Chemical class 0.000 description 5
• 229940104230 thymidine Drugs 0.000 description 5
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
• 229920002307 Dextran Polymers 0.000 description 4
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 4
• 108090000978 Interleukin-4 Proteins 0.000 description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
• 108060001084 Luciferase Proteins 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 210000001744 T-lymphocyte Anatomy 0.000 description 4
• 210000004241 Th2 cell Anatomy 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
• 229920002678 cellulose Polymers 0.000 description 4
• 239000001913 cellulose Substances 0.000 description 4
• 235000010980 cellulose Nutrition 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 230000002349 favourable effect Effects 0.000 description 4
• 239000000945 filler Substances 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 4
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 229960001375 lactose Drugs 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 210000004072 lung Anatomy 0.000 description 4
• 229920000609 methyl cellulose Polymers 0.000 description 4
• 235000010981 methylcellulose Nutrition 0.000 description 4
• 239000001923 methylcellulose Substances 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 244000052769 pathogen Species 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 239000003380 propellant Substances 0.000 description 4
• 150000003230 pyrimidines Chemical class 0.000 description 4
• 238000012552 review Methods 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 239000000600 sorbitol Substances 0.000 description 4
• 125000006850 spacer group Chemical group 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 229960004793 sucrose Drugs 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 241000416162 Astragalus gummifer Species 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 102000019034 Chemokines Human genes 0.000 description 3
• 108010012236 Chemokines Proteins 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 108010002616 Interleukin-5 Proteins 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
• 229920001615 Tragacanth Polymers 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 239000003599 detergent Substances 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 238000012377 drug delivery Methods 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 201000002491 encephalomyelitis Diseases 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 210000000936 intestine Anatomy 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 210000002540 macrophage Anatomy 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 230000001717 pathogenic effect Effects 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 229920001282 polysaccharide Polymers 0.000 description 3
• 239000005017 polysaccharide Substances 0.000 description 3
• 150000004804 polysaccharides Chemical class 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 230000002685 pulmonary effect Effects 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000011257 shell material Substances 0.000 description 3
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
• 210000004989 spleen cell Anatomy 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 229940113082 thymine Drugs 0.000 description 3
• 230000003442 weekly effect Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
• STGXGJRRAJKJRG-JDJSBBGDSA-N (3r,4r,5r)-5-(hydroxymethyl)-3-methoxyoxolane-2,4-diol Chemical group CO[C@H]1C(O)O[C@H](CO)[C@H]1O STGXGJRRAJKJRG-JDJSBBGDSA-N 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• JBLRZGPPMIKPMT-STAMCERTSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methoxy-5-methyl-1,3-diazinane-2,4-dione Chemical compound O=C1NC(=O)C(OC)(C)CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 JBLRZGPPMIKPMT-STAMCERTSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• CKZJTNZSBMVFSU-UBKIQSJTSA-N 4-amino-5-hydroxy-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(O)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKZJTNZSBMVFSU-UBKIQSJTSA-N 0.000 description 2
• OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
• CKZJTNZSBMVFSU-UHFFFAOYSA-N 5-hydroxydeoxycytidine Natural products C1=C(O)C(N)=NC(=O)N1C1OC(CO)C(O)C1 CKZJTNZSBMVFSU-UHFFFAOYSA-N 0.000 description 2
• RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 2
• 208000026872 Addison Disease Diseases 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 108020000946 Bacterial DNA Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 2
• 102000004533 Endonucleases Human genes 0.000 description 2
• 108010042407 Endonucleases Proteins 0.000 description 2
• 239000001856 Ethyl cellulose Substances 0.000 description 2
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• 206010018378 Glomerulonephritis rapidly progressive Diseases 0.000 description 2
• 229930186217 Glycolipid Natural products 0.000 description 2
• 208000024869 Goodpasture syndrome Diseases 0.000 description 2
• 208000008899 Habitual abortion Diseases 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 230000005353 IP-10 production Effects 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• 108090000176 Interleukin-13 Proteins 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 208000003250 Mixed connective tissue disease Diseases 0.000 description 2
• 101100260758 Mus musculus Tlr9 gene Proteins 0.000 description 2
• 206010034277 Pemphigoid Diseases 0.000 description 2
• 241000721454 Pemphigus Species 0.000 description 2
• 208000008469 Peptic Ulcer Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• 230000006044 T cell activation Effects 0.000 description 2
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000000217 alkyl group Chemical group 0.000 description 2
• 125000005600 alkyl phosphonate group Chemical group 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 208000007502 anemia Diseases 0.000 description 2
• 230000003367 anti-collagen effect Effects 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
• 229960000686 benzalkonium chloride Drugs 0.000 description 2
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 208000000594 bullous pemphigoid Diseases 0.000 description 2
• 159000000007 calcium salts Chemical class 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 235000014633 carbohydrates Nutrition 0.000 description 2
• 125000002091 cationic group Chemical group 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000007906 compression Methods 0.000 description 2
• 230000006835 compression Effects 0.000 description 2
• 239000000039 congener Substances 0.000 description 2
• 201000005637 crescentic glomerulonephritis Diseases 0.000 description 2
• 230000016396 cytokine production Effects 0.000 description 2
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
• NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 210000001198 duodenum Anatomy 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• 235000019325 ethyl cellulose Nutrition 0.000 description 2
• 229920001249 ethyl cellulose Polymers 0.000 description 2
• 102000013165 exonuclease Human genes 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 229940029575 guanosine Drugs 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical group 0.000 description 2
• IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical group OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 210000002865 immune cell Anatomy 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 230000003053 immunization Effects 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 229960001438 immunostimulant agent Drugs 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 208000000509 infertility Diseases 0.000 description 2
• 231100000535 infertility Toxicity 0.000 description 2
• 230000036512 infertility Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 229940057995 liquid paraffin Drugs 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229940071648 metered dose inhaler Drugs 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
• 230000000813 microbial effect Effects 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 208000011906 peptic ulcer disease Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
• 239000004810 polytetrafluoroethylene Substances 0.000 description 2
• 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 2
• 201000008171 proliferative glomerulonephritis Diseases 0.000 description 2
• 230000001681 protective effect Effects 0.000 description 2
• ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 238000011282 treatment Methods 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
• 229940029284 trichlorofluoromethane Drugs 0.000 description 2
• ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 238000002255 vaccination Methods 0.000 description 2
• 229960005486 vaccine Drugs 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• 239000000277 virosome Substances 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
• IZUAHLHTQJCCLJ-UHFFFAOYSA-N (2-chloro-1,1,2,2-tetrafluoroethyl) hypochlorite Chemical compound FC(F)(Cl)C(F)(F)OCl IZUAHLHTQJCCLJ-UHFFFAOYSA-N 0.000 description 1
• BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
• XIIAYQZJNBULGD-UHFFFAOYSA-N (5alpha)-cholestane Natural products C1CC2CCCCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 XIIAYQZJNBULGD-UHFFFAOYSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• OHMHBGPWCHTMQE-UHFFFAOYSA-N 2,2-dichloro-1,1,1-trifluoroethane Chemical compound FC(F)(F)C(Cl)Cl OHMHBGPWCHTMQE-UHFFFAOYSA-N 0.000 description 1
• PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical compound NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
• VLEIUWBSEKKKFX-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O VLEIUWBSEKKKFX-UHFFFAOYSA-N 0.000 description 1
• OTDJAMXESTUWLO-UUOKFMHZSA-N 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-oxolanyl]-3H-purine-6-thione Chemical compound C12=NC(N)=NC(S)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OTDJAMXESTUWLO-UUOKFMHZSA-N 0.000 description 1
• HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
• FTBBGQKRYUTLMP-UHFFFAOYSA-N 2-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C1=CC=CN1 FTBBGQKRYUTLMP-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical compound N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 1
• GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
• CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
• VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
• RNLZVUVMQXRIHF-QXFUBDJGSA-N 4-(ethylamino)-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(NCC)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 RNLZVUVMQXRIHF-QXFUBDJGSA-N 0.000 description 1
• MJEQLGCFPLHMNV-UHFFFAOYSA-N 4-amino-1-(hydroxymethyl)pyrimidin-2-one Chemical compound NC=1C=CN(CO)C(=O)N=1 MJEQLGCFPLHMNV-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• SSXTZOXCLZAFDI-CCGCGBOQSA-N 4-amino-1-[(2r,4s,5r)-2,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@]1(O)O[C@H](CO)[C@@H](O)C1 SSXTZOXCLZAFDI-CCGCGBOQSA-N 0.000 description 1
• HMUOMFLFUUHUPE-XLPZGREQSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(hydroxymethyl)pyrimidin-2-one Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 HMUOMFLFUUHUPE-XLPZGREQSA-N 0.000 description 1
• HKRMBQLRJZQTBZ-UHFFFAOYSA-N 5,5-dimethyl-1,3,4-thiadiazinane 1,1-dioxide Chemical compound CC1(C)CS(=O)(=O)CNN1 HKRMBQLRJZQTBZ-UHFFFAOYSA-N 0.000 description 1
• BISHACNKZIBDFM-UHFFFAOYSA-N 5-amino-1h-pyrimidine-2,4-dione Chemical compound NC1=CNC(=O)NC1=O BISHACNKZIBDFM-UHFFFAOYSA-N 0.000 description 1
• ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
• JDBGXEHEIRGOBU-UHFFFAOYSA-N 5-hydroxymethyluracil Chemical compound OCC1=CNC(=O)NC1=O JDBGXEHEIRGOBU-UHFFFAOYSA-N 0.000 description 1
• LMEHJKJEPRYEEB-UHFFFAOYSA-N 5-prop-1-ynylpyrimidine Chemical compound CC#CC1=CN=CN=C1 LMEHJKJEPRYEEB-UHFFFAOYSA-N 0.000 description 1
• VKKXEIQIGGPMHT-UHFFFAOYSA-N 7h-purine-2,8-diamine Chemical compound NC1=NC=C2NC(N)=NC2=N1 VKKXEIQIGGPMHT-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 208000035657 Abasia Diseases 0.000 description 1
• 206010000234 Abortion spontaneous Diseases 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
• 210000004366 CD4-positive T-lymphocyte Anatomy 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 229920001661 Chitosan Polymers 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 239000004380 Cholic acid Substances 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• KKZFLSZAWCYPOC-VPENINKCSA-N Deoxyribose 5-phosphate Chemical compound O[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KKZFLSZAWCYPOC-VPENINKCSA-N 0.000 description 1
• 201000003066 Diffuse Scleroderma Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102400000686 Endothelin-1 Human genes 0.000 description 1
• 101800004490 Endothelin-1 Proteins 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 229920003136 Eudragit® L polymer Polymers 0.000 description 1
• 229920003137 Eudragit® S polymer Polymers 0.000 description 1
• 108060002716 Exonuclease Proteins 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
• 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
• 102000002265 Human Growth Hormone Human genes 0.000 description 1
• 108010000521 Human Growth Hormone Proteins 0.000 description 1
• 239000000854 Human Growth Hormone Substances 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• 241000186660 Lactobacillus Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 108010000817 Leuprolide Proteins 0.000 description 1
• 241000239218 Limulus Species 0.000 description 1
• SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 1
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• 241000316144 Macrodon ancylodon Species 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 235000019759 Maize starch Nutrition 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000244206 Nematoda Species 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
• 108010047956 Nucleosomes Proteins 0.000 description 1
• QWZRZYWLWTWVLF-UHFFFAOYSA-N O.OP(O)=O Chemical compound O.OP(O)=O QWZRZYWLWTWVLF-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 229920001363 Polidocanol Polymers 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004952 Polyamide Substances 0.000 description 1
• 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
• 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
• 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
• 229920000037 Polyproline Polymers 0.000 description 1
• 229920001219 Polysorbate 40 Polymers 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 229920002642 Polysorbate 65 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• 102000004389 Ribonucleoproteins Human genes 0.000 description 1
• 108010081734 Ribonucleoproteins Proteins 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• 239000004147 Sorbitan trioleate Substances 0.000 description 1
• PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 235000015125 Sterculia urens Nutrition 0.000 description 1
• 240000001058 Sterculia urens Species 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
• WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102100040247 Tumor necrosis factor Human genes 0.000 description 1
• 206010046865 Vaccinia virus infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• YLVXPXINUWURSG-UHFFFAOYSA-N [hydroxy(phenyl)methyl]phosphonic acid Chemical compound OP(=O)(O)C(O)C1=CC=CC=C1 YLVXPXINUWURSG-UHFFFAOYSA-N 0.000 description 1
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
• 229910001573 adamantine Inorganic materials 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 150000003838 adenosines Chemical class 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000012387 aerosolization Methods 0.000 description 1
• 229940040563 agaric acid Drugs 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001413 amino acids Chemical group 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229960004977 anhydrous lactose Drugs 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
• 239000003831 antifriction material Substances 0.000 description 1
• 230000030741 antigen processing and presentation Effects 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 244000144974 aquaculture Species 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• 238000000889 atomisation Methods 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• 235000013361 beverage Nutrition 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 239000004067 bulking agent Substances 0.000 description 1
• CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 229910000394 calcium triphosphate Inorganic materials 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000009134 cell regulation Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 229920006184 cellulose methylcellulose Polymers 0.000 description 1
• WZNRVWBKYDHTKI-UHFFFAOYSA-N cellulose, acetate 1,2,4-benzenetricarboxylate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.OC(=O)C1=CC(C(=O)O)=CC=C1C(=O)OCC1C(OC2C(C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(COC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)O2)OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)O1 WZNRVWBKYDHTKI-UHFFFAOYSA-N 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229920001429 chelating resin Polymers 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• XIIAYQZJNBULGD-LDHZKLTISA-N cholestane Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 XIIAYQZJNBULGD-LDHZKLTISA-N 0.000 description 1
• BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
• 235000019416 cholic acid Nutrition 0.000 description 1
• 229960002471 cholic acid Drugs 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• 208000017760 chronic graft versus host disease Diseases 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 229940009976 deoxycholate Drugs 0.000 description 1
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
• KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
• 239000005547 deoxyribonucleotide Substances 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• BOKOVLFWCAFYHP-UHFFFAOYSA-N dihydroxy-methoxy-sulfanylidene-$l^{5}-phosphane Chemical compound COP(O)(O)=S BOKOVLFWCAFYHP-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
• SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 229960002143 fluorescein Drugs 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229910021485 fumed silica Inorganic materials 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 230000002949 hemolytic effect Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 230000028996 humoral immune response Effects 0.000 description 1
• 230000004727 humoral immunity Effects 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000005965 immune activity Effects 0.000 description 1
• 239000012642 immune effector Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 230000002134 immunopathologic effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 229940060367 inert ingredients Drugs 0.000 description 1
• 239000012678 infectious agent Substances 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 210000001630 jejunum Anatomy 0.000 description 1
• 229940039696 lactobacillus Drugs 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 229950006462 lauromacrogol 400 Drugs 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 230000021633 leukocyte mediated immunity Effects 0.000 description 1
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
• 229960004338 leuprorelin Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 229940127554 medical product Drugs 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 239000007932 molded tablet Substances 0.000 description 1
• 230000016379 mucosal immune response Effects 0.000 description 1
• CPQCSJYYDADLCZ-UHFFFAOYSA-N n-methylhydroxylamine Chemical compound CNO CPQCSJYYDADLCZ-UHFFFAOYSA-N 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 230000023837 negative regulation of proteolysis Effects 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 229940023146 nucleic acid vaccine Drugs 0.000 description 1
• 210000001623 nucleosome Anatomy 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 230000001151 other effect Effects 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 230000000505 pernicious effect Effects 0.000 description 1
• 210000001539 phagocyte Anatomy 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
• 150000008300 phosphoramidites Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920002647 polyamide Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
• 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
• 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
• 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 108010026466 polyproline Proteins 0.000 description 1
• 229940101027 polysorbate 40 Drugs 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 229940099511 polysorbate 65 Drugs 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229920002744 polyvinyl acetate phthalate Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• QYDQVHWTOPFKGP-UHFFFAOYSA-N prop-1-yne;pyrimidine Chemical compound CC#C.C1=CN=CN=C1 QYDQVHWTOPFKGP-UHFFFAOYSA-N 0.000 description 1
• ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
• KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• PSHHQIGKVLIVBD-UHFFFAOYSA-N purine-2,4-diamine Chemical compound C1=NC(N)=NC2(N)N=CN=C21 PSHHQIGKVLIVBD-UHFFFAOYSA-N 0.000 description 1
• 150000003220 pyrenes Chemical class 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• 229940100486 rice starch Drugs 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 230000007781 signaling event Effects 0.000 description 1
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
• 235000021309 simple sugar Nutrition 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical group [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
• 239000011775 sodium fluoride Substances 0.000 description 1
• 235000013024 sodium fluoride Nutrition 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000012439 solid excipient Substances 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 235000019337 sorbitan trioleate Nutrition 0.000 description 1
• 229960000391 sorbitan trioleate Drugs 0.000 description 1
• 239000008347 soybean phospholipid Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 150000003408 sphingolipids Chemical class 0.000 description 1
• 108010068698 spleen exonuclease Proteins 0.000 description 1
• 208000000995 spontaneous abortion Diseases 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000009495 sugar coating Methods 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
• MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 125000005591 trimellitate group Chemical group 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 229940124931 vaccine adjuvant Drugs 0.000 description 1
• 239000012646 vaccine adjuvant Substances 0.000 description 1
• 208000007089 vaccinia Diseases 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000012178 vegetable wax Substances 0.000 description 1
• 229940070384 ventolin Drugs 0.000 description 1
• 230000006648 viral gene expression Effects 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 230000007279 water homeostasis Effects 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229940100445 wheat starch Drugs 0.000 description 1